Is DOK5 p.Leu293Arg (c.878T>G) pathogenic?

DOK5 p.Leu293Arg (c.878T>G) is classified Uncertain significance in DOK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.1137); Ultra-rare (popmax 0.0433%, amr).

How common is DOK5 p.Leu293Arg (c.878T>G) in the general population?

DOK5 p.Leu293Arg (c.878T>G) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

What do computational predictors say about DOK5 p.Leu293Arg (c.878T>G)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

DOK5 p.Leu293Arg

c.878T>G · rs201718507 · VCV2592211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -7.51	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 175 kb · p 0.31 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0433% Admixed American · 26/59,996 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.0182% 293/1,613,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0433%	2,308
European (non-Finnish)	0.0216%	4,628
Remaining individualsnot grpmax-eligible	0.0176%	5,681
Finnishnot grpmax-eligible	0.00156%	63,994

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DOK5
Protein: p.Leu293Arg
Coding: c.878T>G
MANE Select: NM_018431
dbSNP: rs201718507
Type: single nucleotide variant
Location: chr20:54650436 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.32 · 1 PDB

Full DOK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK5 p.Ala34Thr Uncertain significance ★★ ⚠ same type
DOK5 p.Ala34Pro Uncertain significance ★ ⚠ same type
DOK5 p.Arg185Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Trp Uncertain significance ★ ⚠ same type
DOK5 p.Arg236Leu Uncertain significance ★ ⚠ same type
DOK5 p.Arg253Trp Uncertain significance ★ ⚠ same type
DOK5 p.Asn117Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dok5-p-leu293arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown